Further investigation of the formation of thyroglobulin will be undertaken with emphasis on the genetic transcript coding for the protein moiety. Thyroid tissue will be obtained from test animals undergoing hormonal or chemical stimulation of thyroglobulin synthesis. Isolation of the thyroid messenger RNAs will proceed from standard methods for separation of the polysomal fractions through the recently developed filtration procedure for specific separation of animal cell messenger RNAs. The messenger RNAs will be distributed by sedimentation and gel electrophoresis and identity of fractions containing thyroglobulin mRNA established through analysis of the translation product using specific immunologic testing. Characterization of genetic and metabolic parameters of the RNA will be studied with the aid of in vitro I125 derivatization labeling. These studies will entail the use of nucleic acid hybridization of labeled thyroglobulin mRNA to determine chromosomal specificity, factors regulating turnover, transport and to test for deletion of the gene(s) in patients lacking detectable thyroglobulin.